@article{79ad97be9659447fa777c5303708a7a2,
title = "Pax6 dosage requirements in iris and ciliary body differentiation",
abstract = "Pax6 is a highly conserved transcription factor that controls the morphogenesis of various organs. Changes in Pax6 dosage have been shown to affect the formation of multiple tissues. PAX6 haploinsufficiency leads to aniridia, a pan-ocular disease primarily characterized by iris hypoplasia. Herein, we employ a modular system that includes null and overexpressed conditional alleles of Pax6. The use of the Tyrp2-Cre line, active in iris and ciliary body (CB) primordium, enabled us to investigate the effect of varying dosages of Pax6 on the development of these ocular sub-organs. Our findings show that a lack of Pax6 in these regions leads to dysgenesis of the iris and CB, while heterozygosity impedes growth of the iris and maturation of the iris sphincter. Overexpression of the canonical, but not the alternative splice variant of Pax6 results in severe structural aberrations of the CB and hyperplasia of the iris sphincter. A splice variant-specific rescue experiment revealed that both splice variants are able to correct iris hypoplasia, while only the canonical form rescues the sphincter. Overall, these findings demonstrate the dosage-sensitive roles of Pax6 in the formation of both the CB and the iris.",
keywords = "Alternative splicing, Ciliary body, Cre/loxP, Eye, Gene dosage, Iris, Pax6, Pax6-5a, Sphincter muscle",
author = "Noa Davis and Chen Yoffe and Shaul Raviv and Ran Antes and Joachim Berger and Silvia Holzmann and Anastassia Stoykova and Overbeek, {Paul A.} and Tamm, {Ernst R.} and Ruth Ashery-Padan",
note = "Funding Information: We are grateful to Peter Gruss for the mouse lines that were established in his laboratory and to Corinne Lobe and Andreas Nagy for the Z/AP reporter line. We also would like to thank Margit Schimmel for excellent technical help with the SEM. Research in R.A.-P.'s laboratory is supported by the Israel Science Foundation, Binational Science Foundation, AMN foundation, Martier Foundation, the Glaucoma Research Foundation, Israeli Ministry of Health, and E. Matilda Ziegler Foundation. N.D.'s research is supported by the Shtacher Foundation and the Israeli Ministry of Science. E.RT.'s research is supported by the German Research Council (FOR 1075, TP5). ",
year = "2009",
month = sep,
day = "1",
doi = "10.1016/j.ydbio.2009.06.023",
language = "אנגלית",
volume = "333",
pages = "132--142",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Elsevier Inc.",
number = "1",
}